a study to investigate the safety, tolerability, and pharmacokinetics of kyn-5356 in healthy subjects aged 18 to 55 years

Conditions: Cognitive Dysfunction; Schizophrenia

Summary: this first-in-human clinical trial with a randomized, double-blind, placebo-controlled, dose-escalation study design is regarded as standard to test the safety, tolerability, and pharmacokinetics of kyn-5356. the study comprises 3 parts: part 1: single ascending dose study part 2: multiple ascending dose study part 3: food effect study the aim of parts 1 and 2 of the study is to evaluate the safety and tolerability following single and multiple ascending doses of kyn-5356. the secondary aim is to evaluate the pharmacokinetics (pk) of escalating single and multiple doses of kyn-5356. in part 2, cerebrospinal fluid will be sampled to explore pk and pharmacodynamic effects of kyn-5356. the potential effect of food intake on the disposition of kyn-5356 following a single oral dose will be evaluated in part 3. part 3 is an open-label, randomized, 2 period, 2 sequence design.


Eligibility criteria:
inclusion criteria: * subject understands the study procedures and agrees to participate by providing written informed consent prior to any study procedures. * subject is between 18 and 55 years of age (inclusive), on the date of signing the informed consent form. * subject has a body mass index between 18 and 30 kg/m2, inclusive. * a female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential or a woman of childbearing potential who agrees to follow the contraceptive guidance (highly effective birth control method) from screening until end of the study. note: males should use appropriate contraceptive method from screening until end of the study. * subject is judged to be in good health by the principal investigator based upon the results of a medical history, physical examination, vital signs, 12-lead ecg, and clinical laboratory safety tests. * subject is willing to adhere to the study requirements and restrictions. exclusion criteria: * subject has positive serology for hbsag, hcv, or hiv, or history of hepatitis from any cause with the exception of hepatitis a that was resolved at least 3 months prior to first dosing of the investigational medicinal product. * subject has any illness judged by the principal investigator as clinically significant, in the 3 months prior to first dosing of the investigational medicinal product. * subject has a suicidality score of "yes" on item 4 or item 5 of the suicidal ideation section of the c-ssrs, if this ideation occurred in the past 6 months, or "yes" on any item of the suicidal behavior section, except for the "non-suicidal self-injurious behavior" (item also included in the suicidal behavior section), if this behavior occurred in the past 2 years. * subject has a history or current sign or symptom of psychiatric or neurologic disease. * subject has a history of head trauma in the past year and/or current seizures. * subject is a smoker (use of tobacco products in the previous 3 months from screening) or uses nicotine or nicotine-containing products and has a positive urine cotinine test at screening or admission. * subject has a history of alcohol and/or illicit drug abuse within 2 years of entry or has a positive screening test for alcohol and/or drugs of abuse at screening or admission. * subject consumes caffeine containing beverages exceeding 500 mg caffeine per day (5 cups of coffee) during the off-site days during the study. * subject has regular excessive consumption of alcohol within 6 months prior to screening (7 drinks/week for females, 14 drinks/week for males where 1 drink = 150 ml of wine or 360 ml of beer or 45 ml of hard liquor). * subject has a history or current sign or symptom of a cardiovascular, renal, or metabolic bone disease or disease of bone remodeling, or any history of endocrine disease, including an abnormal laboratory result for pre-specified clinical laboratory safety parameters related to these conditions. * subject has a history or presence of clinically significant abnormalities detected on 12-lead ecg of either rhythm or conduction. a first-degree atrioventricular block will not be considered as a significant abnormality. subject has qtcf \> 450 ms (mean values per parameter will be considered) detected on the 12-lead ecg at screening or admission. * presence or sequelae of gastrointestinal, liver, kidney (creatinine clearance \<85 ml/min, using the cockcroft-gault formula), or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs at screening or admission. * subject has a history of malignancy within the past 5 years prior to screening with the exception of excised and curatively treated non-metastatic cell carcinoma of the skin which is considered cured with minimal risk of recurrence. * subject tests positive for sars-cov-2 at admission. * additional exclusion criteria for subjects in the mad part in view of lumbar puncture for cerebrospinal fluid (csf) sampling and the erp assessment. * subject uses any prescription drugs, herbal supplements, within 4 weeks prior to initial dosing, and/or over-the-counter medication, dietary supplements (vitamins included) within 2 weeks prior to initial dosing, other than what is allowed per protocol. * subject received vaccination 1 month before admission or plans to receive vaccination during the study. * use of other investigational drugs/devices within 5 half-lives of the drug from enrollment (time of the subject signing the informed consent form), or within 30 days, whichever is longer. * donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing. * plasma donation (\> 200 ml) within 7 days prior to first dosing. * resting vital signs at screening (blood pressure \> 140/90 mmhg, heart rate \> 90 beats per minute, respiratory rate \> 20 breaths per minute, and clinically significant elevated body temperature), or any clinically significant abnormalities in vital signs requiring intervention in the opinion of the investigator. up to 2 repeat measurements are permitted to confirm eligibility.